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Purpose Supplementation with dietary forms of vitamin D is commonplace in clinical medicine, elite athletic cohorts, and the general population, yet the response of all major vitamin D metabolites to high doses of vitamin D is poorly characterized. We aimed to identify the responses of all major vitamin D metabolites to moderate- and high-dose supplemental vitamin D3.

Methods A repeated-measures design was implemented in which 46 elite professional European athletes were block randomized based on their basal 25[OH]D concentration into two treatment groups. Athletes received either 35,000 or 70,000 IU·wk−1 vitamin D3 for 12 wk, and 42 athletes completed the trial. Blood samples were collected for 18 wk to monitor the response to supplementation and withdrawal from supplementation.

Results Both doses led to significant increases in serum 25[OH]D, and 1,25[OH]2D3. 70,000 IU·wk−1 also resulted in a significant increase of the metabolite 24,25[OH]2D at weeks 6 and 12 that persisted after supplementation withdrawal at week 18, despite a marked decrease in 1,25[OH]2D3. Intact parathyroid hormone was decreased in both groups by week 6 and remained suppressed throughout the trial.

Conclusions High-dose vitamin D3 supplementation (70,000 IU·wk−1) may be detrimental for its intended purposes because of increased 24,25[OH]2D production. Rapid withdrawal from high-dose supplementation may inhibit the bioactivity of 1,25[OH]2D3 as a consequence of sustained increases in 24,25[OH]2D that persist as 25[OH]D and 1,25[OH]2D concentrations decrease. These data imply that lower doses of vitamin D3 ingested frequently may be most appropriate and gradual withdrawal from supplementation as opposed to rapid withdrawal may be favorable.

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1Research Institute for Sport and Exercise Science, Liverpool John Moores University, Liverpool, UNITED KINGDOM; 2Faculty of Medicine and Health Science, Norwich Medical School, University of East Anglia. Norwich, UNITED KINGDOM; and 3Department of Sport and Physical Activity, Edge Hill University, Ormskirk, UNITED KINGDOM

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